We have identified specific fine structure DNA repair phenotypes characteristic of a group of related heritable cancer prone and progeroid human syndromes. In Werner's lymphoblastoid cell lines we detect a deficiency in transcription coupled repair, and this represents the first finding of a DNA repair deficiency in Werner cells. This human mutant has several clinical manifestations concordant with normal human aging and is associated with an increased cancer incidence. Alzheimer's disease also provides a useful model system in which to study the role of DNA repair in a condition associated with senescence. We have measured gene-specific repair in fibroblasts from patients with familial and sporadically occurring Alzheimer's disease. Telomeric shortening is one of the age-associated genetic instabilities currently believed to be an important biomarker of aging and cancer. We have measured DNA damage induction and repair in human telomeres and suspect that DNA repair capacity in telomeres may be related to the genomic instability associated with normal human aging and perhaps with tumorigenesis. We find that telomerase activity is increased in the early S-phase of the cell cycle.